Download Progesterone Therapy as a Technique to Reduce Preterm Birth in

Progesterone Therapy as a Technique to Reduce Preterm Birth in
High-Risk Pregnancies
Policy Number:
MM.03.005
Line(s) of Business:
HMO; PPO; QUEST
Section:
OB/GYN & Reproduction
Place(s) of Service:
Outpatient
Original Effective Date:
06/01/2012
Current Effective Date:
03/22/2013
I. Description
Preterm birth is the leading cause of neonatal morbidity and mortality, and effective primary
preventive interventions have remained elusive. In recent years, there has been renewed interest
in the use of progesterone (injectable and intravaginal formulations) to prevent preterm birth.
Preterm labor and delivery are major determinants of neonatal morbidity and mortality. In the U.S.,
the rate of preterm birth is 12%. A variety of diagnostic and prophylactic measures have been
investigated including home uterine activity monitoring, subcutaneous terbutaline tocolytic
therapy, and routine culture and antibiotic treatment of subclinical bacterial vaginosis. To date,
none of these had made a significant demonstrable impact on the incidence of preterm delivery. In
the past, intramuscular injections of hydroxyprogesterone caproate (i.e., Delalutin) were used
routinely to prevent premature labor. However, the drug was shown to have teratogenic
properties, and the U.S. Food and Drug Administration (FDA) labeled the drug as Category D (i.e.,
studies have demonstrated fetal risk, but use of the drug may outweigh the potential risk).
Delalutin is no longer marketed.
In recent years, there has been renewed research interest in intramuscular injection of 17 alphahydroxyprogesterone caproate (17P). 17P is a weakly acting, naturally occurring progesterone
metabolite, which when coupled with caproate dextran works as a long-acting progestin when
administered intramuscularly. 17P has been manufactured locally by compounding pharmacies.
After an extended application process, Makena®, another injectable form of 17P was approved by
the FDA in February 2011. Intravaginal progesterone gel and suppositories have also been used.
On February 3, 2011, an injectable formulation containing 17-alpha-hydroxyprogesterone caproate
was approved by the FDA through the premarket approval process. The product is called Makena
Progesterone Therapy as a Technique to Reduce Preterm Birth in High-Risk Pregnancies
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and will be marketed by KV Pharmaceuticals. It is indicated to reduce preterm birth in women with
a singleton pregnancy who have a history of singleton spontaneous preterm birth. Makena is not
intended for use in women with multiple gestations or in women with other risk factors for
preterm birth.
II. Criteria/Guidelines
Progesterone therapy is covered as follows (subject to Limitations/Exclusions and Administrative
Guidelines):
A. Weekly injections of 17 alpha-hydroxyprogesterone caproate, performed in the office setting,
initiated between 16 and 20 weeks of gestation and continued until 36 weeks 6 days are
covered for women with a prior history of spontaneous preterm birth* before 37 weeks’
gestation.
B. Daily vaginal progesterone between 24 and 34 weeks of gestation is covered for women with a
prior history of spontaneous preterm birth* before 37 weeks’ gestation.
C. Daily vaginal progesterone initiated between 20 and 23 weeks 6 days of gestation and
continued until 36 weeks 6 days is covered for women with a short cervix (less than 20 mm).
*Spontaneous preterm birth is defined as birth due to spontaneous preterm labor or preterm
premature rupture of the fetal membranes. Preterm birth due to infection, uterine anomaly,
multiple gestation, polyhydramnios, abruption placenta, placenta previa or trauma do not meet the
definition of spontaneous preterm birth for the use of 17P.
Note: It should be noted that appropriate training of certified ultrasonographers with ongoing
quality assurance programs are considered critical to the accurate measurement of cervical length
in the second trimester.
III. Limitations/Exclusions
Progesterone therapy as a technique to prevent preterm delivery does not meet payment
determination criteria in pregnant women with other risk factors for preterm delivery, including
but not limited to multiple gestations, or positive tests for cervicovaginal fetal fibronectin, cervical
cerclage, or a uterine anomaly.
IV. Administrative Guidelines
A. Precertification is required for Makena. To precertify, please complete HMSA's Precertification
Request and mail or fax the form as indicated.
B. Precertification is not required for other forms of 17P. HMSA reserves the right to perform
retrospective review using the above criteria to validate if services rendered met payment
determination criteria.
C. QUEST members must obtain the drug through a participating pharmacy.
D. Applicable codes
Progesterone Therapy as a Technique to Reduce Preterm Birth in High-Risk Pregnancies
CPT
96372
Description
Therapeutic, prophylactic, or diagnostic injection (specify substance or
drug); subcutaneous or intramuscular
HCPCS
J1725
Description
Injection, hydroxyprogesterone caproate, 1 mg (new code effective
1/1/12)
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V. Important Reminder
The purpose of this Medical Policy is to provide a guide to coverage. This Medical Policy is not
intended to dictate to providers how to practice medicine. Nothing in this Medical Policy is
intended to discourage or prohibit providing other medical advice or treatment deemed
appropriate by the treating physician.
Benefit determinations are subject to applicable member contract language. To the extent there
are any conflicts between these guidelines and the contract language, the contract language will
control.
This Medical Policy has been developed through consideration of the medical necessity criteria
under Hawaii’s Patients’ Bill of Rights and Responsibilities Act (Hawaii Revised Statutes §432E-1.4),
generally accepted standards of medical practice and review of medical literature and government
approval status. HMSA has determined that services not covered under this Medical Policy will not
be medically necessary under Hawaii law in most cases. If a treating physician disagrees with
HMSA’s determination as to medical necessity in a given case, the physician may request that
HMSA reconsider the application of the medical necessity criteria to the case at issue in light of any
supporting documentation.
VI. References
1. Dodd JM, Flenady V, Cincotta R et al. Prenatal administration of progesterone for preventing
preterm birth. Cochrane Database Syst Rev 2006; (1):CD004947.
2. Rode L, Langhoff-Roos J, Andersson C et al. Systematic review of progesterone for the
prevention of preterm birth in singleton pregnancies. Acta Obstect Gynecol 2009; 88(11):11809.
3. Tita AT, Rouse DJ. Progesterone for preterm birth prevention: an evolving intervention. Am J
Obstet Gynecol 2009; 200(3):219-24.
4. Dodd JM, Crowther CA. The role of progesterone in prevention of preterm birth. Int J Womens
Health 2010; 1:73-84.
5. Meis PJ, Klebanoff M, Thom E et al. Prevention of recurrent preterm delivery by 17 alphahydroxyprogesterone caproate. N Engl J Med 2003; 348(24):2379-85.
6. Northen AT, Norman GS, Anderson K et al.; National Institute of Child Health and Human
Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network. Follow-up of children
Progesterone Therapy as a Technique to Reduce Preterm Birth in High-Risk Pregnancies
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exposed in utero to 17 alpha-hydroxyprogesterone caproate compared with placebo. Obstet
Gynecol 2007; 110(4):865-72.
7. da Fonseca EB, Bittar RE, Carvalho MH et al. Prophylactic administration of progesterone by
vaginal suppository to reduce the incidence of spontaneous preterm birth in women at
increased risk: a randomized placebo-controlled double-blind study. Am J Obstet Gynecol 2003;
188(2):419-24.
8. O'Brien JM, Adair CD, Lewis DF et al. Progesterone vaginal gel for the reduction of recurrent
preterm birth: primary results from a randomized, double-blind, placebo-controlled trial.
Ultrasound Obstet Gynecol 2007; 30(5):687-96.
9. Majhi P, Bagga R, Kalra J et al. Intravaginal use of natural micronized progesterone to prevent
pre-term birth: a randomized trial in India. J Obstet Gynecol 2009; 29(6):493-8.
10. Berghella V, Figueroa D, Szychowski JM et al. 17-alpha-hydroxyprogesterone caproate for the
prevention of preterm birth in women with prior preterm birth and a short cervical length. Am J
Obstet Gynecol 2010; 202(4):351, e1-6.
11. Fonseca EB, Celik E, Parra M et al; Fetal Medicine Foundation Second Trimester Screening
Group. Progesterone and the risk of preterm birth among women with a short cervix. N Engl J
Med 2007; 357(5):462-9.
12. Hassan SS, Romero R, Vidyadhari D et al. Vaginal progesterone reduces the rate of preterm
birth in women with a sonographic short cervix: a multicenter, randomized, double-blind,
placebo-controlled trial. Ultrasound Obstet Gynecol 2011 [Epub before print].
13. DeFranco EA, O'Brien JM, Adair CD et al. Vaginal progesterone is associated with a decrease in
risk for early preterm birth and improved neonatal outcome in women with a short cervix: a
secondary analysis from a randomized, double-blind, placebo-controlled trial. Ultrasound
Obstet Gynecol 2007; 30(5):697-705.
14. Briery CM, Veillon EW, Klauser CK et al. Women with premature rupture of the membranes do
not benefit from weekly progesterone. Am J Obstet Gynecol 2011; 204(1):54.e1-5.
15. Rouse DJ, Caritis SN, Peaceman AM et al.; National Institute of Child Health and Human
Development Maternal-Fetal Medicine Units Network. A trial of 17 alpha-hydroxyprogesterone
caproate to prevent prematurity in twins. N Engl J Med 2007; 357(5):454-61.
16. Norman JE, Mackenzie F, Owen P et al. Progesterone for the prevention of preterm birth in twin
pregnancy (STOPPIT): a randomized, double-blind, placebo-controlled study and meta-analysis.
Lancet 2009; 373(9680):2034-40.
17. Caritis SN, Rouse DJ, Peaceman AM et al.; Eunice Kennedy Shriver National Institute of Child
Health and Human Development (NICHD), Maternal-Fetal Medicine Units Network (MFMU).
Prevention of preterm birth in triplets using 17 alpha-hydroxyprogesterone caproate: a
randomized controlled trial. Obstet Gynecol 2009; 113(2 pt 1):285-92.
18. American College of Obstetricians and Gynecologists’ Committee on Obstetric Practice and the
Society for Maternal Fetal Medicine. Use of Progesterone to Reduce Preterm Birth. ACOG
Committee Opinion Number 419 (replaces No. 291, November 2003). Obstet Gynecol 2008:
112(4):963-5.
19. Comparing IM vs. vaginal progesterone for pre-term birth (NCT00579553). Sponsored by the
University of Oklahoma. Last updated June 12, 2012. Available online at: ClinicalTrials.gov . Last
accessed January 2013.
Progesterone Therapy as a Technique to Reduce Preterm Birth in High-Risk Pregnancies
20. RCT of progesterone to prevent preterm birth in nulliparous women with a short cervix (SCAN)
(NCT00439374). Sponsored by the National Institute of Child Health and Human Development.
Last updated October 26, 2012. Available online at: ClinicalTrials.gov . Last accessed January
2013.
21. Blue Cross Blue Shield Association. Progesterone Therapy as a Technique to Reduce Preterm
Birth in High-Risk Pregnancies. 4.01.16; September 2012.
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